title: Prevalence and risk of preexisting heparin-induced thrombocytopenia antibodies in patients with acute VTE.
abstract: BACKGROUND
  Some patients with acute VTE who may previously have been exposed to heparin products have unrecognized antibodies implicated in heparin-induced thrombocytopenia (HIT). Antibody prevalence and patient consequences upon exposure to heparin, low-molecular-weight heparin, and fondaparinux are uncertain.
  
  
  METHODS
  In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. We compared the risk of HIT (> 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. Comparison groups for thrombocytopenia occurrence comprised patients with ELISA-positive, platelet-activating, antibody-positive results; ELISA-positive, but platelet-activating antibody-negative results; and randomly selected antibody-negative results.
  
  
  RESULTS
  A total of 127 of 3,994 patients (3.2%) had ELISA-positive results at baseline, but only 14 (0.4%; 95% CI, 0.2%-0.6%) had platelet-activating antibodies. Among these 14, four treated with unfractionated or low-molecular-weight heparin developed HIT compared with zero of 10 fondaparinux-treated patients (OR, 95; 95% CI, 8-1,123; P < .001). This frequency (four of four, 100%) significantly differed from that of both heparin-treated patients whose results were ELISA positive but platelet-activating antibody negative and from heparin-treated antibody-negative control subjects (zero of 15 and zero of 27, respectively; P < .001 for both).
  
  
  CONCLUSIONS
  Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT.
authors.affiliation: Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.affiliation: University of Washington School of Medicine, Seattle, WA. Electronic address: brucedavidson@pobox.com.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Davidson
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.affiliation: Flinders Medical Center, Adelaide, SA, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gallus
authors.affiliation: Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Gent
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Anthonie W A
authors.initials: AWA
authors.lastname: Lensing
authors.affiliation: Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Piovella
authors.affiliation: University Hospital of Maastricht, Maastricht, The Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Annelise E M
authors.initials: AEM
authors.lastname: Segers
authors.affiliation: Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Kelton
mesh_terms: D000208:Acute Disease; D000906:Antibodies / Q000097:blood*; D000925:Anticoagulants / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D000077425:Fondaparinux; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D010978:Platelet Factor 4 / Q000276:immunology*; D011134:Polysaccharides / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D010978:Platelet Factor 4; D006493:Heparin; D000077425:Fondaparinux